Abstract
Background Congenital hyperinsulinism (CHI) is a rare and life-threatening genetic disorder. Sirolimus as a mammalian target of rapamycin inhibitor may be helpful in patients with CHI who do not respond well to other treatments including diazoxide and octreotide. However, the safety and efficacy of this therapy are still unclear. This study aimed to evaluate the potential therapeutic effects of sirolimus in CHI patients with mutations in the ABCC8 and KCNJ11 genes. Methods During the period of this follow-up study, every child with a confirmed diagnosis of unresponsive CHI underwent genetic evaluation. Among those who had positive genetic testing, six families agreed to participate in this study. The participants were evaluated for ABCC8, KCNJ11, or HNF4α gene mutations by polymerase chain reaction (PCR) sequencing. The participants who were unresponsive to diazoxide and octreotide therapy received 0.5 mg/m2/d of sirolimus, and the dose was gradually increased until a serum concentration of 5–15 ng/ml was achieved. Then, the participants were followed up for any possible complications. Results Among the study participants, only one neonate was completely free of hypoglycemia after one year of follow-up, whereas three others experienced a partial reduction in hypoglycemic episodes over six months. One neonate underwent pancreatectomy despite receiving sirolimus. The oldest participant with a mutation in the ABCC8 gene responded well to sirolimus therapy after surgery and remained asymptomatic for 18 months. Conclusion This study suggested that sirolimus therapy needs further evaluation to determine which patients will benefit the most. The genetic basis of CHI may have possible implications for determining the patient's response.
Highlights
Self-limiting hypoglycemia is a common problem that occurs shortly after birth and is managed by regular feeding or dextrose-containing intravenous fluids
All of them were termed at the time of delivery, 2 patients were large for gestational age (LGA) and one patient was small for gestational age (SGA)
The patients 2, 4, and 6 agreed to undergo a DOPA positron emission tomography (PET) scan (Figure 1). e PET scan for our patients showed suspicious lesions in the head of the pancreas. e age of disease onset, as well as sirolimus administration, is demonstrated in Table 2, and the plasma glucose level was evaluated every 4–6 hours. e recommended blood glucose target of >70 mg/dl had a margin of safety for the goal of treatment and reducing neurological complications
Summary
Self-limiting hypoglycemia is a common problem that occurs shortly after birth and is managed by regular feeding or dextrose-containing intravenous fluids. Is study aimed to evaluate the potential therapeutic effects of sirolimus in CHI patients with mutations in the ABCC8 and KCNJ11 genes. During the period of this follow-up study, every child with a confirmed diagnosis of unresponsive CHI underwent genetic evaluation. Among those who had positive genetic testing, six families agreed to participate in this study. E participants who were unresponsive to diazoxide and octreotide therapy received 0.5 mg/m2/d of sirolimus, and the dose was gradually increased until a serum concentration of 5–15 ng/ml was achieved. E oldest participant with a mutation in the ABCC8 gene responded well to sirolimus therapy after surgery and remained asymptomatic for 18 months. Conclusion. is study suggested that sirolimus therapy needs further evaluation to determine which patients will benefit the most
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